tbuckley/cabot-search huggingface dataset:
Association of Potentially Damaging De Novo Gene Variants With Neurologic Outcomes in Congenital Heart Disease
Authors: Sarah U. Morton, Ami Norris-Brilliant, Sean Cunningham, Eileen King, Elizabeth Goldmuntz, Martina Brueckner, Thomas A. Miller, Nina H. Thomas, Chunyan Liu, Heather R. Adams, David C. Bellinger, John Cleveland, James F. Cnota, Anders M. Dale, Michele Frommelt, Bruce D. Gelb, P. Ellen Grant, Caren S. Goldberg, Hao Huang, Joshua M. Kuperman, Jennifer S. Li, Patrick S. McQuillen, Ashok Panigrahy, George A. Porter, Amy E. Roberts, Mark W. Russell, Christine E. Seidman, Madalina E. Tivarus, Evdokia Anagnoustou, Donald J. Hagler, Wendy K. Chung, Jane W. Newburger
Journal: JAMA Network Open (2023)

Neurodevelopmental disabilities are commonly associated with congenital heart disease (CHD), but medical and sociodemographic factors explain only one-third of the variance in outcomes.
AMPK Phosphorylates ZDHHC13 to Increase MC1R Activity and Suppress Melanomagenesis
Authors: Yu Sun, Xin Li, Chengqian Yin, Judy Zhang, Ershang Liang, Xianfang Wu, Ying Ni, Joshua Arbesman, Colin R. Goding, Shuyang Chen
Journal: Cancer Research (2023)

Abstract Inherited genetic variations in the melanocortin-1 receptor (MC1R) responsible for human red hair color (RHC) variants are associated with impaired DNA damage repair and increased melanoma risk. MC1R signaling is critically dependent on palmitoylation, primarily mediated by the protein acyltransferase zinc finger DHHC-type palmitoyltransferase 13 (ZDHHC13). A better understanding of how ZDHHC13 is physiologically activated could help identify approaches to prevent melanomagenesis in redheads. Here, we report that AMP-activated protein kinase (AMPK) phosphorylates ZDHHC13 at S208 to strengthen the interaction between ZDHHC13 and MC1R-RHC, leading to enhanced MC1R palmitoylation in redheads. Consequently, phosphorylation of ZDHHC13 by AMPK increased MC1R-RHC downstream signaling. AMPK activation and MC1R palmitoylation repressed UVB-induced transformation of human melanocytes in vitro and delayed melanomagenesis in vivo in C57BL/6J-MC1R-RHC mice. The importance of AMPK to MC1R signaling was validated in human melanomas where AMPK upregulation correlated with expression of factors downstream from MC1R signaling and with prolonged patient survival. These findings suggest AMPK activation as a promising strategy to reduce melanoma risk, especially for individuals with red hair. Significance: Phosphorylation of ZDHHC13 by AMPK at S208 promotes MC1R activation and suppresses melanocyte transformation, indicating activation of AMPK as a potential approach to prevent melanoma in people with red hair.
First-line Immunotherapy and Clinically Meaningful Survival Benefits for the Oldest Adults With Lung Cancer
Authors: Marjory Charlot, Jhanelle E. Gray
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Prevalence of Undiagnosed Diabetes Identified by a Novel Electronic Medical Record Diabetes Screening Program in an Urban Emergency Department in the US
Authors: Kirstie K. Danielson, Brett Rydzon, Milena Nicosia, Anjana Maheswaren, Yuval Eisenberg, Janet Lin, Brian T. Layden
Journal: JAMA Network Open (2023)

This cross-sectional study describes a screening program that was developed to screen for type 2 diabetes in an urban emergency department setting in the US.
Association of Neural Connectome With Early Experiences of Abuse in Adults
Authors: Mayuresh S. Korgaonkar, Isabella A. Breukelaar, Kim Felmingham, Leanne M. Williams, Richard A. Bryant
Journal: JAMA Network Open (2023)

Importance More than 10% of children experience sexual, physical, or emotional abuse, and abuse experienced during sensitive neurodevelopmental periods is associated with a greater risk of psychiatric disorders. Objective To investigate the extent to which a history of abuse is associated with alterations in the intrinsic functional connectome of the adult brain independent from the restriction of associated psychiatric conditions. Design, Setting, and Participants This cohort study assessed data from 768 adult participants from the greater Sydney, Australia, area who were included in the study without diagnostic restrictions and categorized based on a history of childhood sexual, physical, and/or emotional abuse. Data were collected from January 1, 2009, to December 31, 2015; data analysis was performed from October 1, 2020, to March 31, 2022. Main Outcomes and Measures Outcomes were structured psychiatric interview responses, self-report of the frequency and extent of various types of negative experiences in childhood and adolescence, and intrinsic functional connectivity derived from 5 functional magnetic resonance imaging tasks and estimated among 436 brain regions, comprising intranetwork and internetwork connectivity of 8 large-scale brain networks. Results Among the 647 individuals with usable data (330 female [51.0%]; mean [SD] age, 33.3 [12.0] years; age range, 18.2-69.2 years), history of abuse was associated with greater likelihood of a current psychiatric illness (odds ratio, 4.55; 95% CI, 3.07-6.72; P &amp;amp;lt; .001) and with greater depressive, anxiety, and stress symptoms (mean difference, 20.4; 95% CI, 16.1-24.7; P &amp;amp;lt; .001). An altered connectome signature of higher connectivity within somatomotor, dorsal, and ventral attention networks and between these networks and executive control and default mode networks was observed in individuals with a history of abuse experienced during childhood (n = 127) vs those without a history of abuse (n = 442; mean difference, 0.07; 95% CI, 0.05-0.08; familywise, Bonferroni-corrected P = .01; Cohen d = 0.82) and compared with those who experienced abuse in adolescence (n = 78; mean difference, 0.06; 95% CI, 0.04-0.08]; familywise, Bonferroni-corrected P &amp;amp;lt; .001; Cohen d = 0.68). Connectome alterations were not observed for those who experienced abuse in adolescence. Connectivity of this signature was transdiagnostic and independent of the nature and frequency of abuse, sex, or current symptomatic state. Conclusions and Relevance Findings highlight the associations of exposure to abuse before and during adolescence with the whole-brain functional connectome. The experience of child abuse was found to be associated with physiologic changes in intrinsic connectivity, independent of psychopathology, in a way that may affect functioning of systems responsible for perceptual processing and attention.
Trends in Outpatient Visits and Hospital and Intensive Care Unit Admissions of Adults With COVID-19 in an Integrated US Health Care System, March 2020 to January 2022
Authors: Laura C. Myers, Kevin Ng, Colleen Plimier, Kathleen A. Daly, Patricia Kipnis, Vincent X. Liu
Journal: JAMA Network Open (2023)

This cohort study of patients at a single integrated health system examines trends in COVID-19–related treatment location and mortality.
Household Transmission of Influenza A Viruses in 2021-2022
Authors: Melissa A. Rolfes, H. Keipp Talbot, Huong Q. McLean, Melissa S. Stockwell, Katherine D. Ellingson, Karen Lutrick, Natalie M. Bowman, Emily E. Bendall, Ayla Bullock, James D. Chappell, Jessica E. Deyoe, Julie Gilbert, Natasha B. Halasa, Kimberly E. Hart, Sheroi Johnson, Ahra Kim, Adam S. Lauring, Jessica T. Lin, Christopher J. Lindsell, Son H. McLaren, Jennifer K. Meece, Alexandra M. Mellis, Miriana Moreno Zivanovich, Constance E. Ogokeh, Michelle Rodriguez, Ellen Sano, Raul A. Silverio Francisco, Jonathan E. Schmitz, Celibell Y. Vargas, Amy Yang, Yuwei Zhu, Edward A. Belongia, Carrie Reed, Carlos G. Grijalva
Journal: JAMA (2023)

Influenza virus infections declined globally during the COVID-19 pandemic. Loss of natural immunity from lower rates of influenza infection and documented antigenic changes in circulating viruses may have resulted in increased susceptibility to influenza virus infection during the 2021-2022 influenza season.To compare the risk of influenza virus infection among household contacts of patients with influenza during the 2021-2022 influenza season with risk of influenza virus infection among household contacts during influenza seasons before the COVID-19 pandemic in the US.This prospective study of influenza transmission enrolled households in 2 states before the COVID-19 pandemic (2017-2020) and in 4 US states during the 2021-2022 influenza season. Primary cases were individuals with the earliest laboratory-confirmed influenza A(H3N2) virus infection in a household. Household contacts were people living with the primary cases who self-collected nasal swabs daily for influenza molecular testing and completed symptom diaries daily for 5 to 10 days after enrollment.Household contacts living with a primary case.Relative risk of laboratory-confirmed influenza A(H3N2) virus infection in household contacts during the 2021-2022 season compared with prepandemic seasons. Risk estimates were adjusted for age, vaccination status, frequency of interaction with the primary case, and household density. Subgroup analyses by age, vaccination status, and frequency of interaction with the primary case were also conducted.During the prepandemic seasons, 152 primary cases (median age, 13 years; 3.9% Black; 52.0% female) and 353 household contacts (median age, 33 years; 2.8% Black; 54.1% female) were included and during the 2021-2022 influenza season, 84 primary cases (median age, 10 years; 13.1% Black; 52.4% female) and 186 household contacts (median age, 28.5 years; 14.0% Black; 63.4% female) were included in the analysis. During the prepandemic influenza seasons, 20.1% (71/353) of household contacts were infected with influenza A(H3N2) viruses compared with 50.0% (93/186) of household contacts in 2021-2022. The adjusted relative risk of A(H3N2) virus infection in 2021-2022 was 2.31 (95% CI, 1.86-2.86) compared with prepandemic seasons.Among cohorts in 5 US states, there was a significantly increased risk of household transmission of influenza A(H3N2) in 2021-2022 compared with prepandemic seasons. Additional research is needed to understand reasons for this association.
Association Between Age and Survival Trends in Advanced Non–Small Cell Lung Cancer After Adoption of Immunotherapy
Authors: Teja Voruganti, Pamela R. Soulos, Ronac Mamtani, Carolyn J. Presley, Cary P. Gross
Journal: JAMA Oncology (2023)

Importance The introduction of immune checkpoint inhibitors (ICIs) has transformed the care of advanced non–small cell lung cancer (NSCLC). Although clinical trials suggest substantial survival benefits, it is unclear how outcomes have changed in clinical practice. Objective To assess temporal trends in ICI use and survival among patients with advanced NSCLC across age strata. Design, Setting, and Participants This cohort study was performed in approximately 280 predominantly community-based US cancer clinics and included patients aged 18 years or older who had stage IIIB, IIIC, or IV NSCLC diagnosed between January 1, 2011, and December 31, 2019, with follow-up through December 31, 2020. Data were analyzed April 1, 2021, to October 19, 2022. Main Outcomes and Measures Median overall survival and 2-year survival probability. The predicted probability of 2-year survival was calculated using a mixed-effects logit model adjusting for demographic and clinical characteristics. Results The study sample included 53 719 patients (mean [SD] age, 68.5 [9.3] years; 28 374 men [52.8%]), the majority of whom were White individuals (36 316 [67.6%]). The overall receipt of cancer-directed therapy increased from 69.0% in 2011 to 77.2% in 2019. After the first US Food and Drug Administration approval of an ICI for NSCLC, the use of ICIs increased from 4.7% in 2015 to 45.6% in 2019 ( P &amp;amp;lt; .001). Use of ICIs in 2019 was similar between the youngest and oldest patients (aged &amp;amp;lt;55 years, 45.2% vs aged ≥75 years, 43.8%; P = .59). From 2011 to 2018, the predicted probability of 2-year survival increased from 37.7% to 50.3% among patients younger than 55 years and from 30.6% to 36.2% in patients 75 years or older ( P &amp;amp;lt; .001). Similarly, median survival in patients younger than 55 years increased from 11.5 months to 16.0 months during the study period, while survival among patients 75 years or older increased from 9.1 months in 2011 to 10.2 months in 2019. Conclusions and Relevance This cohort study found that, among patients with advanced NSCLC, the uptake of ICIs after US Food and Drug Administration approval was rapid across all age groups. However, corresponding survival gains were modest, particularly in the oldest patients.
Rechallenge After Oxaliplatin-Induced Hypersensitivity Reactions
Authors: Elie Rassy, Florence Le Roy, Cristina Smolenschi, Marine Valéry, Valérie Boige, Michel Ducreux, Alice Boilève
Journal: JAMA Oncology (2023)

This cohort study assesses the outcome of oxaliplatin desensitization for patients with gastrointestinal cancers who experienced hypersensitivity reactions after oxaliplatin infusion.
Overall Survival With Adjuvant mFOLFIRINOX for Pancreatic Cancer
Authors: Michele Reni, Marina Macchini, Luca Porcu
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Overall Survival With Adjuvant mFOLFIRINOX for Pancreatic Cancer—Reply
Authors: Thierry Conroy, Florence Castan, Pascal Hammel
Journal: JAMA Oncology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Erratum. 10. Cardiovascular disease and risk management: <i>Standards of Care in Diabetes—2023</i>. Diabetes Care 2023;46(Suppl. 1):S158–S190
Authors: Nuha A. ElSayed, Grazia Aleppo, Vanita R. Aroda, Raveendhara R. Bannuru, Florence M. Brown, Dennis Bruemmer, Billy S. Collins, Sandeep R. Das, Marisa E. Hilliard, Diana Isaacs, Eric L. Johnson, Scott Kahan, Kamlesh Khunti, Mikhail Kosiborod, Jose Leon, Sarah K. Lyons, Mary Lou Perry, Priya Prahalad, Richard E. Pratley, Jane Jeffrie Seley, Robert C. Stanton, Robert A. Gabbay
Journal: Diabetes Care (2023)

Fig. 10.2 of the article cited above provides recommendations for the treatment of confirmed hypertension in people with diabetes. Due to a composition error, the initial blood pressure range for the left side of the algorithm was given as ≥140/90 and &amp;lt;160/100 mmHg; the correct initial blood pressure range is ≥130/80 and &amp;lt;160/100 mmHg. The online version of the article (https://doi.org/10.2337/dc23-S010) has been updated to correct the error.
Plasma Amino Acids in Early Pregnancy and Midpregnancy and Their Interplay With Phospholipid Fatty Acids in Association With the Risk of Gestational Diabetes Mellitus: Results From a Longitudinal Prospective Cohort
Authors: Jiaxi Yang, Jing Wu, Fasil Tekola-Ayele, Ling-Jun Li, Andrew A. Bremer, Ruijin Lu, Mohammad L. Rahman, Natalie L. Weir, Wei Wei Pang, Zhen Chen, Michael Y. Tsai, Cuilin Zhang
Journal: Diabetes Care (2023)

OBJECTIVE We prospectively evaluated plasma amino acids (AAs) in early pregnancy and midpregnancy and their interplay with phospholipid fatty acids (FAs) in association with gestational diabetes mellitus (GDM) risk. RESEARCH DESIGN AND METHODS From a longitudinal pregnancy cohort of 2,802 individuals, concentrations of 24 plasma AAs at 10–14 and 15–26 gestational weeks (GW) were assessed among 107 GDM case subjects and 214 non-GDM control subjects. We estimated adjusted odds ratios (OR) and 95% CI for the associations of plasma AAs and the joint associations of plasma AAs and phospholipid FAs with GDM risk, adjusting for risk factors including age, prepregnancy BMI, and family history of diabetes. RESULTS Glycine at 10–14 GW was inversely associated with GDM (adjusted OR [95% CI] per SD increment: 0.55 [0.39–0.79]). Alanine, aspartic acid, and glutamic acid at 10–14 GW were positively associated with GDM (1.43 [1.08–1.88], 1.41 [1.11–1.80], and 1.39 [0.98–1.98]). At 15–26 GW, findings for glycine, alanine, aspartic acid, and the glutamine–to–glutamic acid ratio were consistent with the directions observed at 10–14 GW. Isoleucine, phenylalanine, and tyrosine were positively associated with GDM (1.64 [1.19–2.27], 1.15 [0.87–1.53], and 1.56 [1.16–2.09]). All P values for linear trend were &amp;lt;0.05. Several AAs and phospholipid FAs were significantly and jointly associated with GDM. For instance, the lowest risk was observed among women with higher glycine and lower even-chain saturated FAs at 10–14 GW (adjusted OR [95% CI] 0.15 [0.06, 0.37]). CONCLUSIONS Plasma AAs may be implicated in GDM development starting in early pregnancy. Associations of AAs with GDM may be enhanced in the copresence of phospholipid FA profile.
Combined PD-1, BRAF and MEK inhibition in BRAFV600E colorectal cancer: a phase 2 trial
Authors: Jun Tian, Jonathan H. Chen, Sherry X. Chao, Karin Pelka, Marios Giannakis, Julian Hess, Kelly Burke, Vjola Jorgji, Princy Sindurakar, Jonathan Braverman, Arnav Mehta, Tomonori Oka, Mei Huang, David Lieb, Maxwell Spurrell, Jill N. Allen, Thomas A. Abrams, Jeffrey W. Clark, Andrea C. Enzinger, Peter C. Enzinger, Samuel J. Klempner, Nadine J. McCleary, Jeffrey A. Meyerhardt, David P. Ryan, Matthew B. Yurgelun, Katie Kanter, Emily E. Van Seventer, Islam Baiev, Gary Chi, Joy Jarnagin, William B. Bradford, Edmond Wong, Alexa G. Michel, Isobel J. Fetter, Giulia Siravegna, Angelo J. Gemma, Arlene Sharpe, Shadmehr Demehri, Rebecca Leary, Catarina D. Campbell, Omer Yilmaz, Gad A. Getz, Aparna R. Parikh, Nir Hacohen, Ryan B. Corcoran
Journal: Nature Medicine (2023)

Abstract While BRAF inhibitor combinations with EGFR and/or MEK inhibitors have improved clinical efficacy in BRAF V600E colorectal cancer (CRC), response rates remain low and lack durability. Preclinical data suggest that BRAF/MAPK pathway inhibition may augment the tumor immune response. We performed a proof-of-concept single-arm phase 2 clinical trial of combined PD-1, BRAF and MEK inhibition with sparatlizumab (PDR001), dabrafenib and trametinib in 37 patients with BRAF V600E CRC. The primary end point was overall response rate, and the secondary end points were progression-free survival, disease control rate, duration of response and overall survival. The study met its primary end point with a confirmed response rate (24.3% in all patients; 25% in microsatellite stable patients) and durability that were favorable relative to historical controls of BRAF-targeted combinations alone. Single-cell RNA sequencing of 23 paired pretreatment and day 15 on-treatment tumor biopsies revealed greater induction of tumor cell-intrinsic immune programs and more complete MAPK inhibition in patients with better clinical outcome. Immune program induction in matched patient-derived organoids correlated with the degree of MAPK inhibition. These data suggest a potential tumor cell-intrinsic mechanism of cooperativity between MAPK inhibition and immune response, warranting further clinical evaluation of optimized targeted and immune combinations in CRC. ClinicalTrials.gov registration: NCT03668431.
APOBEC mutagenesis is a common process in normal human small intestine
Authors: Yichen Wang, Philip S. Robinson, Tim H. H. Coorens, Luiza Moore, Henry Lee-Six, Ayesha Noorani, Mathijs A. Sanders, Hyunchul Jung, Riku Katainen, Robert Heuschkel, Roxanne Brunton-Sim, Robyn Weston, Debbie Read, Beverley Nobbs, Rebecca C. Fitzgerald, Kourosh Saeb-Parsy, Iñigo Martincorena, Peter J. Campbell, Simon Rushbrook, Matthias Zilbauer, Simon James Alexander Buczacki, Michael R. Stratton
Journal: Nature Genetics (2023)

Abstract APOBEC mutational signatures SBS2 and SBS13 are common in many human cancer types. However, there is an incomplete understanding of its stimulus, when it occurs in the progression from normal to cancer cell and the APOBEC enzymes responsible. Here we whole-genome sequenced 342 microdissected normal epithelial crypts from the small intestines of 39 individuals and found that SBS2/SBS13 mutations were present in 17% of crypts, more frequent than most other normal tissues. Crypts with SBS2/SBS13 often had immediate crypt neighbors without SBS2/SBS13, suggesting that the underlying cause of SBS2/SBS13 is cell-intrinsic. APOBEC mutagenesis occurred in an episodic manner throughout the human lifespan, including in young children. APOBEC1 mRNA levels were very high in the small intestine epithelium, but low in the large intestine epithelium and other tissues. The results suggest that the high levels of SBS2/SBS13 in the small intestine are collateral damage from APOBEC1 fulfilling its physiological function of editing APOB mRNA.